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"Zhang, Hui"
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LncRNA CAIF inhibits autophagy and attenuates myocardial infarction by blocking p53-mediated myocardin transcription
Increasing evidence suggests that long noncoding RNAs (lncRNAs) play crucial roles in various biological processes. However, little is known about the effects of lncRNAs on autophagy. Here we report that a lncRNA, termed cardiac autophagy inhibitory factor (CAIF), suppresses cardiac autophagy and attenuates myocardial infarction by targeting p53-mediated myocardin transcription. Myocardin expression is upregulated upon H
2
O
2
and ischemia/reperfusion, and knockdown of myocardin inhibits autophagy and attenuates myocardial infarction. p53 regulates cardiomyocytes autophagy and myocardial ischemia/reperfusion injury by regulating myocardin expression. CAIF directly binds to p53 protein and blocks p53-mediated myocardin transcription, which results in the decrease of myocardin expression. Collectively, our data reveal a novel CAIF-p53-myocardin axis as a critical regulator in cardiomyocyte autophagy, which will be potential therapeutic targets in treatment of defective autophagy-associated cardiovascular diseases.
Little is known about the role of long lncRNAs in autophagy. The authors identify lncCAIF, and show that it suppresses cardiac autophagy and attenuates myocardial infarction by targeting p53 -mediated transcription of myocardin.
Journal Article
Cognitive load as a mediator in self-efficacy and English learning motivation among vocational college students
Chinese vocational colleges, under global and educational pressures, encounter challenges in IT integration for English teaching, which risks dampening student motivation due to heightened cognitive load. This study addresses the need to elucidate the mediating role of cognitive load in the relationship between self-efficacy and learning motivation among these students. By integrating Social Cognitive Theory(SCT) and Cognitive Load Theory(CLT), the research employs a structural equation model to analyze survey data, revealing that self-efficacy positively impacts deep and achievement motivation and negatively influences cognitive load, which in turn affects learning motivation. These insights underscore the importance of fostering self-efficacy and managing cognitive load to enhance vocational students’ English learning motivation, offering valuable guidance for educational practices and curriculum development in the face of global challenges.
Journal Article
Fuzzy comprehensive evaluation and quantitative weight analysis in structure management of human resources
This research delves into the application effects of Fuzzy Comprehensive Evaluation (FCE) and quantitative weight analysis in the structure management of human resources (SMHR) to optimize the structure management. The research begins by analyzing the existing problems in SMHR, such as incomplete performance feedback and error-prone outsourcing decisions. By leveraging human resource management (HRM) characteristics, the researchers construct the SMHR evaluation index system. The Analytical Hierarchy Process (AHP) is employed to establish a hierarchical human resource structure model to determine the relative weight of each HRM indicator. Subsequently, the FCE method is utilized to build an SMHR optimization model, which is then scrutinized and assessed by means of an example. The findings indicate that the consistency ratio ( C . R .) values of the first and second-level evaluation factors of the constructed model are less than 0.1, thus passing the consistency test and demonstrating credibility. Ultimately, the research effectively grades SMHR in the enterprise through the analysis of HRM optimization. Accordingly, this research presents a set of optimization suggestions and measures, including the establishment of a professional HRM operation team, acceleration of the construction of a professional talent team, enhancement of the intelligent level of the HRM center, and transition towards digital sharing. These proposed measures can serve as valuable experimental references for the optimization and improvement of HRM structures in future enterprises.
Journal Article
UCHL3 promotes ovarian cancer progression by stabilizing TRAF2 to activate the NF-κB pathway
The inflammatory response plays an important role in carcinogenesis. However, the functional role and mechanism of the UCHL3-associated inflammatory response in ovarian cancer remain to be characterized. Here, we report that increased expression of UCHL3 facilitates tumourigenesis by targeting TRAF2 protein, thereby enhancing the inflammatory response. The expression of UCHL3 is elevated in ovarian cancer patients and is associated with an unfavourable prognosis. Genetic ablation of UCHL3 was found to markedly block ovarian cancer cell proliferation, viability and migration both in vitro and in vivo. Mechanistically, luciferase pathway screening results show that NF-κB signalling is clearly activated compared with other pathways. UCHL3 was found to activate NF-κB signalling by deubiquitinating and stabilizing TRAF2, leading to tumourigenesis. Our results indicate that highly expressed UCHL3 enhances inflammation by stabilizing TRAF2, which in turn facilitates tumourigenesis in ovarian cancer, and that UCHL3 is a potential target for ovarian cancer patients with increased inflammation.
Journal Article
Regulation of DNA Replication Licensing and Re-Replication by Cdt1
In eukaryotic cells, DNA replication licensing is precisely regulated to ensure that the initiation of genomic DNA replication in S phase occurs once and only once for each mitotic cell division. A key regulatory mechanism by which DNA re-replication is suppressed is the S phase-dependent proteolysis of Cdt1, an essential replication protein for licensing DNA replication origins by loading the Mcm2-7 replication helicase for DNA duplication in S phase. Cdt1 degradation is mediated by CRL4Cdt2 ubiquitin E3 ligase, which further requires Cdt1 binding to proliferating cell nuclear antigen (PCNA) through a PIP box domain in Cdt1 during DNA synthesis. Recent studies found that Cdt2, the specific subunit of CRL4Cdt2 ubiquitin E3 ligase that targets Cdt1 for degradation, also contains an evolutionarily conserved PIP box-like domain that mediates the interaction with PCNA. These findings suggest that the initiation and elongation of DNA replication or DNA damage-induced repair synthesis provide a novel mechanism by which Cdt1 and CRL4Cdt2 are both recruited onto the trimeric PCNA clamp encircling the replicating DNA strands to promote the interaction between Cdt1 and CRL4Cdt2. The proximity of PCNA-bound Cdt1 to CRL4Cdt2 facilitates the destruction of Cdt1 in response to DNA damage or after DNA replication initiation to prevent DNA re-replication in the cell cycle. CRL4Cdt2 ubiquitin E3 ligase may also regulate the degradation of other PIP box-containing proteins, such as CDK inhibitor p21 and histone methylase Set8, to regulate DNA replication licensing, cell cycle progression, DNA repair, and genome stability by directly interacting with PCNA during DNA replication and repair synthesis.
Journal Article
Confidence intervals for low dimensional parameters in high dimensional linear models
The purpose of this paper is to propose methodologies for statistical inference of low dimensional parameters with high dimensional data. We focus on constructing confidence intervals for individual coefficients and linear combinations of several of them in a linear regression model, although our ideas are applicable in a much broader context. The theoretical results that are presented provide sufficient conditions for the asymptotic normality of the proposed estimators along with a consistent estimator for their finite dimensional covariance matrices. These sufficient conditions allow the number of variables to exceed the sample size and the presence of many small non‐zero coefficients. Our methods and theory apply to interval estimation of a preconceived regression coefficient or contrast as well as simultaneous interval estimation of many regression coefficients. Moreover, the method proposed turns the regression data into an approximate Gaussian sequence of point estimators of individual regression coefficients, which can be used to select variables after proper thresholding. The simulation results that are presented demonstrate the accuracy of the coverage probability of the confidence intervals proposed as well as other desirable properties, strongly supporting the theoretical results.
Journal Article
Slimy partners: the mucus barrier and gut microbiome in ulcerative colitis
Ulcerative colitis (UC) is a chronic recurrent intestinal inflammatory disease characterized by high incidence and young onset age. Recently, there have been some interesting findings in the pathogenesis of UC. The mucus barrier, which is composed of a mucin complex rich in O-glycosylation, not only provides nutrients and habitat for intestinal microbes but also orchestrates the taming of germs. In turn, the gut microbiota modulates the production and secretion of mucins and stratification of the mucus layers. Active bidirectional communication between the microbiota and its ‘slimy’ partner, the mucus barrier, seems to be a continually performed concerto, maintaining homeostasis of the gut ecological microenvironment. Any abnormalities may induce a disorder in the gut community, thereby causing inflammatory damage. Our review mainly focuses on the complicated communication between the mucus barrier and gut microbiome to explore a promising new avenue for UC therapy.
Gut microbiome: Slimy symbiosis
Gaining a better understanding of the bidirectional communication between the gut microbiome and the colon’s mucus layer, which covers and protects intestinal tissue, could aid in developing effective treatments for ulcerative colitis (UC). Increasing evidence links gut microbiome imbalance to UC, a form of inflammatory bowel disease. Xiaohong Zhang at Ningbo University in China and co-workers have reviewed gut microbiome–mucus layer interactions. They report that the mucus layer, comprised of a firm sterile inner layer, and a loose, densely colonized outer layer, nourishes and provides a home for ‘good’ microbes, while excluding pathogens. In turn, good microbes promote mucus layer production and stratification. Without adequate dietary fiber, gut microbes over-consume the mucus layer, exposing intestinal tissue and causing inflammation. This article provides clue for investigating treatments for inflammatory bowel diseases, including UC.
Journal Article
Cell-permeable organic fluorescent probes for live-cell long-term super-resolution imaging reveal lysosome-mitochondrion interactions
Characterizing the long-term nanometer-scale interactions between lysosomes and mitochondria in live cells is essential for understanding their functions but remains challenging due to limitations of the existing fluorescent probes. Here, we develop cell-permeable organic fluorescent probes for lysosomes with excellent specificity and high photostability. We also use an existing Atto 647N dye with high brightness and excellent photostability to achieve specific labeling of mitochondria in live cells. Using these probes, we obtain dual-color structured illumination microscopy (SIM) images of dynamic physical lysosome-mitochondrion interactions in live cells at an ~90-nm resolution over a long time course of ~13 min. We successfully record the consecutive dynamic processes of lysosomal fusion and fission, as well as four types of physical lysosome-mitochondrion interactions by super-resolution imaging. Our probes provide an avenue for understanding the functions and the dynamic interplay of lysosomes and mitochondria in live cells.
Studying interactions between lysosomes and mitochondria in living cells is difficult due to the limitations of existing probes. Here, the authors develop new cell-permeable fluorescent probes to image the dynamics of lysosomes and their physical interactions with mitochondria using super-resolution microscopy.
Journal Article
Spin-neutral currents for spintronics
Electric currents carrying a net spin polarization are widely used in spintronics, whereas globally spin-neutral currents are expected to play no role in spin-dependent phenomena. Here we show that, in contrast to this common expectation, spin-independent conductance in compensated antiferromagnets and normal metals can be efficiently exploited in spintronics, provided their magnetic space group symmetry supports a non-spin-degenerate Fermi surface. Due to their momentum-dependent spin polarization, such antiferromagnets can be used as active elements in antiferromagnetic tunnel junctions (AFMTJs) and produce a giant tunneling magnetoresistance (TMR) effect. Using RuO
2
as a representative compensated antiferromagnet exhibiting spin-independent conductance along the [001] direction but a non-spin-degenerate Fermi surface, we design a RuO
2
/TiO
2
/RuO
2
(001) AFMTJ, where a globally spin-neutral charge current is controlled by the relative orientation of the Néel vectors of the two RuO
2
electrodes, resulting in the TMR effect as large as ~500%. These results are expanded to normal metals which can be used as a counter electrode in AFMTJs with a single antiferromagnetic layer or other elements in spintronic devices. Our work uncovers an unexplored potential of the materials with no global spin polarization for utilizing them in spintronics.
Spin-polarised electric currents have been studied extensively for use in spintronics, while their spin-neutral counterparts have been largely ignored. Here Shao et al show that such spin-neutral currents can be controlled by the Neel vector orientation of an antiferromagnet and detected using an antiferromagnetic tunnel junction.
Journal Article